New,Non‐quinone Fluorogeldanamycin Derivatives Strongly Inhibit Hsp90

Streptomyces hygroscopicus is a natural producer of geldanamycin. Mutasynthetic supplementation of an AHBA‐blocked mutant with all possible monofluoro 3‐aminobenzoic acids provided new fluorogeldanamycins. These showed strong antiproliferative activity and inhibitory effects on human heat shock protein Hsp90. Binding to Hsp90 in the low nanomolar range was determined from molecular modelling, AFM analysis and by calorimetric studies.     

Experimental investigation of tornado-like vortex dynamics with swirl ratio: The mean and turbulent flow fields

An experimental simulation of tornado-like vortices is conducted in a small tornado vortex simulator in order to study the effect of swirl ratio on flow characteristics. Particle Image Velocimetry (PIV) method is employed to quantitatively determine the tornado-vortex velocity field for swirl ratios ranging from 0.08 to 1. The radial and tangential components of velocity as well as the core radius of the tornado increase with increase in swirl ratio. The location of the maximum radial and tangential velocities is adjacent to the ground where the tornado vortex interacts with the surface. The values of normal and shear turbulent stresses indicate the existence of a laminar core for small swirl. As expected the shear stresses increase with swirl ratio as the vortex becomes turbulent. The highest turbulent production corresponds to the critical case of vortex touchdown.     

On a numerical strategy to simulate nanotube‐reinforced composite materials

The application of carbon nanotubes as the reinforcing phase in composite materials is considered. A literature review in regards to the simulation approaches that have been done in order to study the behavior of nanotube‐reinforced composites from several aspects is provided. After that, a new approach for investigating the mechanical properties of the composites reinforced with randomly oriented fibers using the finite element method is proposed. The main idea is to create regular shaped islands around the distributed fibers and to connect these islands to each other and to the representative volume element. Two application examples show the flexibility and the reliability of the proposed method. It has been shown that this approach can handle both aligned and arbitrary distributions of the nanotubes.     

Situational constraint effects on performance, affective reactions, and turnover: A field replication and extension.

Administered a demographic questionnaire, ability and personality tests, and measures of job performance, satisfaction, turnover, and situational constraints to 731 20–65 yr old store managers, 555 22–62 yr old supervisors, and 164 25–60 yr old district managers from the same company. Results replicate previous laboratory findings and show that higher situational constraints were associated with lower employee performance. The performance ratings given to managers facing the most severe situational constraints were significantly poorer than those received by managers dealing with lower levels of constraints. The presence of situational constraints is associated with employees expressing greater dissatisfaction and frustration. The group facing the highest level of situational constraints had the highest level of turnover. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exploring the recovery of fatigue damage in bituminous mixtures: the role of rest periods

Recovery capability of bituminous materials plays a significant role in the development of new technologies for extending the service life of asphalt pavements. This capability originates from various phenomena such as thixotropy, cooling, relaxation of hardening, or healing. However, their real effect on mechanical response is not clear. This article aims to investigate how rest periods (RPs) available between traffic loads can contribute to the damage recovery of bituminous materials. For this purpose, different types and durations of RPs were applied during the laboratory evaluation of fatigue resistance of these materials using the University of Granada Fatigue Asphalt Cracking Test method. The results indicate that the addition of RPs to the loading regime could lead to an extension in the fatigue life of bituminous materials. Additionally, an increase in the RP duration showed a positive impact on the resistance of the materials against cyclic loading. Nonetheless, these benefits are not only related to the recovery of lost properties during RPs, but also a growth in the amount of plastic deformations as a result of the applying RPs could delay the appearance of damages (i.e. cracking). Consequently, the bituminous material can tolerate a higher number of load cycles during fatigue test.     

Metal‐Based Nanomaterials in Biomedical Applications: Antimicrobial Activity and Cytotoxicity Aspects

Microbial colonization on material surfaces is ubiquitous. Biofilms derived from surface‐colonized microbes pose serious problems to the society from both an economical perspective and a health concern. Incorporation of antimicrobial nanocompounds within or on the surface of materials, or by coatings, to prevent microbial adhesion or kill the microorganisms after their attachment to biofilms, represents an important strategy in an increasingly challenging field. Over the last decade, many studies have been devoted to preparing meta‐based nanomaterials that possess antibacterial, antiviral, and antifungal activities to combat pathogen‐related diseases. Herein, an overview on the state‐of‐the‐art antimicrobial nanosized metal‐based compounds is provided, including metal and metal oxide nanoparticles as well as transition metal nanosheets. The antimicrobial mechanism of these nanostructures and their biomedical applications such as catheters, implants, medical delivery systems, tissue engineering, and dentistry are discussed. Their properties as well as potential caveats such as cytotoxicity, diminishing efficacy, and induction of antimicrobial resistance of materials incorporating these nanostructures are reviewed to provide a backdrop for future research.     

Advances in Antimicrobial Microneedle Patches for Combating Infections

Skin infections caused by bacteria, viruses and fungi are difficult to treat by conventional topical administration because of poor drug penetration across the stratum corneum. This results in low bioavailability of drugs to the infection site, as well as the lack of prolonged release. Emerging antimicrobial transdermal and ocular microneedle patches have become promising medical devices for the delivery of various antibacterial, antifungal, and antiviral therapeutics. In the present review, skin anatomy and its barriers along with skin infection are discussed. Potential strategies for designing antimicrobial microneedles and their targeted therapy are outlined. Finally, biosensing microneedle patches associated with personalized drug therapy and selective toxicity toward specific microbial species are discussed.     

Antimicrobial Ionic Liquid-Based Materials for Biomedical Applications

Excessive and unwarranted administration of antibiotics has invigorated the evolution of multidrug-resistant microbes. There is, therefore, an urgent need for advanced active compounds. Ionic liquids with short-lived ion-pair structures are highly tunable and have diverse applications. Apart from their unique physicochemical features, the newly discovered biological activities of ionic liquids have fascinated biochemists, microbiologists, and medical scientists. In particular, their antimicrobial properties have opened new vistas in overcoming the current challenges associated with combating antibiotic-resistant pathogens. Discussions regarding ionic liquid derivatives in monomeric and polymeric forms with antimicrobial activities are presented here. The antimicrobial mechanism of ionic liquids and parameters that affect their antimicrobial activities, such as chain length, cation/anion type, cation density, and polymerization, are considered. The potential applications of ionic liquids in the biomedical arena, including regenerative medicine, biosensing, and drug/biomolecule delivery, are presented to stimulate the scientific community to further improve the antimicrobial efficacy of ionic liquids.     

Entropy-based scheduling of resource-constrained construction projects

A method is presented for resource allocation and scheduling of resource-constrained projects by use of a measure of the projects' entropy. The entropy, as a measure of the degree of disorder in a system, is an indicator of a project's tendency to progress out of order and into a chaotic condition and it can thus serve to forecast a project's development. The entropy metric used in the analysis is based on the resource assignments per activity (required vs. assigned resource units).     

Fixed-time sliding mode observer-based controller for a class of uncertain nonlinear double integrator systems

This paper investigates a fixed-time convergence issue using the sliding mode observer-based controller for a class of uncertain nonlinear double integrator systems. This observer-based controller is designed assuming that only the first state measurement is available and there is no information about external disturbances and modeling uncertainties. A new form of sliding mode observer in combination with a sliding mode controller is designed to estimate unmeasured state and unknown disturbances and uncertainties as well as provide the estimated data in the control law. A novel form of sliding surfaces for the robust observer-based controller is proposed for which fixed-time convergence is guaranteed to achieve trajectory tracking. In the proposed fixed-time scheme, the bound on the settling time is user-defined using design parameters regardless of the system's initial conditions. The control law and observer law are designed such that the chattering issue is alleviated in the control signal. The stability analysis of the closed-loop system using the observer-based controller is established via the Lyapunov theory. The validity of the controller design is tested by applying and simulating an example of a robot manipulator in Simulink/MATLAB. The superiority of the proposed method is demonstrated by comparing it with two other methods from the relevant literature.